Tory grandee Ken Clarke is joining forces with Labour peer Lord Mandelson in a historic cross-party bid to turn back the rising tide of Euroscepticism.

The two political heavyweights will share a platform to call for an abandonment of plans to disengage from the European project. Clarke, who attends cabinet as a minister without portfolio, is determined to fight back against the clamour for Britain to step back from the European Union or withdraw entirely.

Along with Liberal Democrat Lord Rennard, Clarke and Mandelson will spearhead a new organisation, the Centre for British Influence through Europe (CBIE), which will support a cross-party "patriotic fightback for British leadership in Europe". The organisation will hold its launch event at the end of the month.

Peter Wilding, director of the CBIE, and a former head of media for the Conservative party in the European parliament, told the Observer: "Both Mandelson and Rennard are closely involved in our policy and campaign strategy. Having them with Ken Clarke on one platform, we think, says something in itself about the need for grown-up, consensual politics on Europe.

"We would argue – and many in the Tory party would agree – that disengagement from Europe is profoundly contrary to Britain's national interests."

The group claims that Eurosceptic plans for repatriation of powers are not supported by practical methods to achieve the objectives, while many proposals could be achieved by negotiating with allies within the system rather than through demands for treaty change. They also warn that an aggressive approach to reform could provoke a damaging backlash from other EU member states.

The Clarke/Mandelson heavyweight alliance comes as an influential group of Eurosceptic Tory MPs privately plans to push the prime minister towards a more radical position on the EU.

A leaked copy of demands to be made to David Cameron by MPs from the Fresh Start group includes the call for the UK to unilaterally break its treaty obligations unless the prime minister achieves a fundamental renegotiation of Britain's relationship with the EU.

The prime minister is adding the finishing touches to a long-awaited speech on Britain's position in Europe, due this month in The Hague. He is expected to promise a referendum during the next parliament to approve a series of significant but limited changes in the UK's relationship with the EU.

The impending speech has prompted high-profile figures on both sides of the argument to stake out their ground. Lord Heseltine yesterday described Downing Street's position as "ill-advised".

The Fresh Start group, led by David Cameron's former press secretary George Eustice MP, will urge the prime minister in the coming days to seek a repatriation of a much more significant swath of powers along with fundamental changes to the way the EU works. They want to take back competences over social and employment laws; negotiate an "emergency brake" allowing the UK to veto future regulation of the financial services; an opt-out from policing and criminal justice measures; and abolition of the Strasbourg seat of the European parliament.

They will tell the prime minister: "The status quo in the European Union is no longer an option. If appropriate reforms cannot be negotiated, the UK should consider unilateral action that would involve breaking treaty obligations."

A letter is also being circulated in Westminster by Eustice and Conservative MP Andrea Leadsom calling for support from MPs, MEPs and peers for their Fresh Start Project Manifesto for Change and "a new relationship with the EU, based on trade and political co-operation". The group is holding a private meeting on Wednesday.

A separate group of Tory MPs, led by Bill Cash MP, who want a straight withdrawal from the EU, will also go public in an attempt to force the prime minister's hand.

Heseltine, a former president of the board of trade and now a government adviser on industrial strategy, spoke of his concerns about Cameron's plans to seek a renegotiation of EU treaties and to offer the public a referendum on the results: "To commit to a referendum about a negotiation that hasn't begun, on a timescale you cannot predict, on an outcome that's unknown, where Britain's appeal as an inward investment market would be the centre of debate, seem to me like an unnecessary gamble."

"There would be people who say I'm being disloyal to the Conservative party in saying these things. I'm being loyal to the self interest of this country".

Sir Roger Carr, president of the CBI, writing on this newspaper's website, also urged caution. "To have influence the UK must be viewed as a committed partner today seeking to constructively create a better future for tomorrow," he said. "It is in no one's interest that the UK is persistently seen as a reluctant player constantly looking for the way out and not the way forward."

• An Opinium/Observer poll shows that while nearly half of the public (48%) would be more likely to support a party offering a referendum on Europe, an almost identical proportion (47%) think that successful renegotiation of Britain's ties to the EU by Cameron is unlikely. Respondents were evenly split on whether leaving the EU would have a significantly negative effect on the UK economy, with 34% agreeing, 33% disagreeing and 24% taking no position.